Axonal polyneuropathy and ataxia in children: consider Perrault Syndrome, a case report

BMC Med Genomics. 2023 Nov 6;16(1):278. doi: 10.1186/s12920-023-01599-4.


Background: Perrault Syndrome (PRLTS) is a rare, autosomal recessive disorder that presents with bilateral sensorineural hearing loss in all patients and gonadal dysfunction in females. It has been linked to variants in CLPP, ERAL1, HARS2, HSD17B4, LARS2, and TWNK genes. All reported cases due to TWNK variants have included neurologic features, such as ataxia and axonal sensorimotor neuropathy.

Case presentation: A 4.5-year-old female presented to neuromuscular clinic due to ataxia. Neurological examination revealed truncal ataxia and steppage gait, reduced deep tendon reflexes, and axonal sensorimotor polyneuropathy. Auditory brainstem response testing revealed an uncommon type of sensorineural hearing loss known as auditory neuropathy/auditory synaptopathy (AN/AS) affecting both ears. Magnetic Resonance Imaging (MRI) revealed subtle cauda equina enhancement. Nerve conduction studies led to a provisional diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP), and intravenous immune globulin (IVIG) was initiated. The patient was unresponsive to treatment, thus whole exome testing (WES) was conducted in tandem with IVIG weaning. WES revealed a compound heterozygous state with two variants in the TWNK gene and a diagnosis of Perrault Syndrome was made.

Conclusions: Perrault Syndrome should be considered in the differential for children who present with bilateral sensorineural hearing loss, axonal polyneuropathy, and ataxia. Further examination includes testing for ovarian dysgenesis and known PRLTS genetic variants.

Keywords: Ataxia; Auditory neuropathy/auditory synaptopathy; Axonal polyneuropathy; PRLTS; Perrault Syndrome; TWNK.

Publication types

  • Case Reports

MeSH terms

  • Amino Acyl-tRNA Synthetases* / genetics
  • Ataxia
  • Child, Preschool
  • Female
  • Hearing Loss, Sensorineural* / genetics
  • Humans
  • Immunoglobulins, Intravenous / genetics
  • Mutation
  • Polyneuropathies*


  • Amino Acyl-tRNA Synthetases
  • Immunoglobulins, Intravenous
  • LARS2 protein, human

Supplementary concepts

  • Gonadal dysgenesis XX type deafness